U.S. patent application number 16/874455 was filed with the patent office on 2020-08-27 for nebulized ethanol for internal disinfecting and improvement.
The applicant listed for this patent is Darren Rubin, Howard Rubin. Invention is credited to Darren Rubin, Howard Rubin.
Application Number | 20200268656 16/874455 |
Document ID | / |
Family ID | 1000004882627 |
Filed Date | 2020-08-27 |
United States Patent
Application |
20200268656 |
Kind Code |
A1 |
Rubin; Darren ; et
al. |
August 27, 2020 |
Nebulized Ethanol for Internal Disinfecting and Improvement
Abstract
Methods of the present disclosure utilize alcohol (e.g.,
ethanol) as an active ingredient or agent for disinfecting,
washing, and/or treating infection in the upper and/or lower
airways. Methods include aerosol inhalation, lung spraying, and/or
lung lavage using ethanol-containing solutions. Such methods can be
applied to complicated pneumonia and respiratory pandemics,
including the COVID-19 pandemic caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2).
Inventors: |
Rubin; Darren; (Largo,
FL) ; Rubin; Howard; (Land O Lakes, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Rubin; Darren
Rubin; Howard |
Largo
Land O Lakes |
FL
FL |
US
US |
|
|
Family ID: |
1000004882627 |
Appl. No.: |
16/874455 |
Filed: |
May 14, 2020 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 45/06 20130101;
A61K 9/08 20130101; A61K 31/045 20130101; A61K 9/0078 20130101 |
International
Class: |
A61K 9/00 20060101
A61K009/00; A61K 31/045 20060101 A61K031/045; A61K 9/08 20060101
A61K009/08 |
Claims
1. A method, comprising: applying an at least one alcohol as a
liquid, solution, or pharmaceutical drug composition to upper
and/or lower airways of a person or animal exposed to an infectious
agent.
2. The method of claim 1, wherein the upper and/or lower airways of
the person or animal exposed to the infectious agent are
disinfected in response to application of the at least one alcohol
to the upper and/or lower airways of the person or animal.
3. The method of claim 1, wherein a viral load in the upper and/or
lower airways of the person or animal exposed to the infectious
agent is reduced in response to application of the at least one
alcohol to the upper and/or lower airways of the person or
animal.
4. The method of claim 1, further comprising treating the person or
animal exposed to the infectious agent via application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
5. The method of claim 1, further comprising reducing or
eliminating blood clots of the person or animal exposed to the
infectious agent in response to application of the at least one
alcohol to the upper and/or lower airways of the person or
animal.
6. The method of claim 1, further comprising improving respiration
of the person or animal exposed to the infectious agent via
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
7. The method of claim 1, further comprising improving oxygen
saturation of the person or animal exposed to the infectious agent
via application of the at least one alcohol to the upper and/or
lower airways of the person or animal.
8. The method of claim 1, further comprising preventing a need for
mechanical ventilation of the person or animal exposed to the
infectious agent via application of the at least one alcohol to the
upper and/or lower airways of the person or animal; or reducing a
length of time the person or animal exposed to the infectious agent
needs mechanical ventilation in response to application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
9. The method of claim 1, wherein the at least one alcohol includes
ethanol, propanol, isopropyl alcohol, phenol, an alcohol
derivative, an alcohol conjugate, or a combination thereof.
10. The method of claim 1, further comprising nebulizing or
aerosolizing the at least one alcohol, or humidifying therapeutic
gas with the at least one alcohol, for application to the upper
and/or lower airways of the person or animal.
11. The method of claim 1, further comprising spraying, dispensing,
or dripping the at least one alcohol for application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
12. The method of claim 1, further comprising performing an
endoscopy, including rhinoscopy, laryngoscopy, bronchoscopy, or a
combination thereof, to apply the at least one alcohol to the upper
and/or lower airways of the person or animal.
13. The method of claim 1, further comprising performing a lavage,
a bronchoalveolar lavage, or a whole lung lavage to apply the at
least one alcohol to the upper and/or lower airways of the person
or animal.
14. The method of claim 1, further comprising removing a majority
of the at least one alcohol from the upper and/or lower airways of
the person or animal after application of the at least one alcohol
to the upper and/or lower airways of the person or animal.
15. The method of claim 1, further comprising removing fluid and/or
mucous from the upper and/or lower airways of the person or animal
after application of the at least one alcohol to the upper and/or
lower airways of the person or animal.
16. The method of claim 1, further comprising intubating the person
or animal exposed to the infectious agent after or during
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
17. The method of claim 1, further comprising diluting the at least
one alcohol prior to application of the at least one alcohol to the
upper and/or lower airways of the person or animal.
18. The method of claim 1, further comprising diluting the at least
one alcohol with water and/or saline prior to application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
19. The method of claim 1, further comprising diluting the at least
one alcohol with a bronchodilator-containing solution,
surfactant-containing solution, or a combination thereof, prior to
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
20. The method of claim 1, further comprising diluting the at least
one alcohol to contain between and including 5% to 95% alcohol or
ethanol prior to application of the at least one alcohol to the
upper and lower airways of the person or animal.
21. The method of claim 1, further comprising diluting the at least
one alcohol to contain from 30% to 70% alcohol or ethanol prior to
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
22. The method of claim 1, further comprising mixing the at least
one alcohol with an at least one additional active pharmaceutical
ingredient and/or active pharmaceutical ingredient formulation
prior to application of the at least one alcohol to the upper
and/or lower airways of the person or animal.
23. The method of claim 1, wherein the at least one alcohol
includes a liquid pharmaceutical drug formulation having an at
least one excipient ingredient and an at least one active
pharmaceutical ingredient.
24. The method of claim 1, further comprising sampling and testing
lung fluid and/or lung secretions for infectious agent
quantitatively and/or qualitatively prior to and/or after
application of the at least one alcohol to the upper and lower
airways of the person or animal.
25. The method of claim 1, wherein the infectious agent includes a
bacteria, fungus, virus, coronavirus, severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), or a combination thereof.
26. The method of claim 1, further comprising applying at least 0.1
mL of the at least one alcohol to the upper and/or lower airways of
the person or animal.
27. The method of claim 1, further comprising applying at least 1
mL of the at least one alcohol to the upper and/or lower airways of
the person or animal.
28. The method of claim 1, further comprising applying the at least
one alcohol to the upper and/or lower airways of the person or
animal using positive-pressure, a positive-pressure device, an
incentive device, an inhalation resistance device, or a combination
thereof.
29. The method of claim 1, wherein the at least one alcohol as a
liquid, solution, or pharmaceutical drug composition comprises at
least 10% alcohol or ethanol.
30. A lung lavage wash solution comprising at least 10% alcohol or
ethanol diluted in saline.
Description
BACKGROUND
[0001] Treatment protocols for viral infections are often specific
to the virus strain, with little efficacy crossover between virus
strains. In some examples, available treatments for one type of
virus strain may be ineffective against a mutation of that virus
strain. As a result, there is often a significant lag between
discovery of an infectious virus strain and an effective treatment
protocol being available. Sometimes the lag can be on the order of
years. For virus strains that pose significant health risks, such
as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
which causes COVID-19 disease, the lack of treatment and prevention
can lead to global pandemics. Technological advancements of viral
treatments may also be held back by the speed at which a virus
mutates. For example, due to a lack of financial return on
investment, research and development of a treatment for a
particular virus strain may be scuttled if the virus strain mutates
to a new, less dangerous strain before the treatment is fully
developed and evaluated. As such, there remains a desire for a more
comprehensive treatment of viral infections.
DETAILED DESCRIPTION
[0002] This disclosure includes methods for treatment of
respiratory viral infections using alcohol (e.g., ethanol) as an
active ingredient or agent for disinfecting, washing, and/or
treating infection in the upper and/or lower airways. The various
methods described herein include aerosol inhalation, lung spraying,
and/or lung lavage using ethanol-containing solutions. Particularly
relevant to the current COVID-19 pandemic, the treatments developed
according to this disclosure may be particularly helpful to
mitigate effects of the SARS-CoV-2 and the COVID-19 disease, which
may result in many lives being saved.
[0003] Alcohol in the healthcare setting generally includes ethyl
alcohol (ethanol) or isopropyl alcohol, yet many other alcohols
exist. Ethanol lock is sometimes used for infusion catheter lines,
e.g., central venous catheter lines. The Centers for Disease
Control (CDC) note that alcohol can be used as a chemical
disinfectant, but point out that alcohols have generally underrated
germicidal characteristics. It is believed that no liquid chemical
sterilant or high-level disinfectant containing alcohol as a main
active ingredient has been cleared by the United States Food and
Drug Administration (FDA). The CDC is aware of hospital infection
outbreaks that have occurred when alcohol was used to disinfect
medical instruments, instead of more effective disinfectants.
Alcohol does not destroy bacterial spores. It is clear to see why
alcohol is not the best disinfectant in the healthcare setting.
[0004] Yet, the methods of the present disclosure utilize alcohol
as an active ingredient or agent for disinfecting and/or treating
infection in the upper and/or lower airways. Ethanol may be used in
some embodiments. Additionally or alternatively, another alcohol
(e.g., isopropyl alcohol) and/or a different virucidal and/or
bactericidal agent may be used. In many embodiments of these
inventive methods, an alcohol product (e.g., a liquid
pharmaceutical drug composition or formulation containing alcohol),
or a dilution or solution thereof, is used. For example, a liquid
pharmaceutical drug product and/or formulation that includes
ethanol (e.g., dehydrated alcohol or dehydrated alcohol injection),
or a dilution or solution thereof, is used. A liquid ethanol
product or solution may be applied to the airways as described
herein for disinfection, reduction of viral load, treatment,
improving lung function, improving oxygen saturation, reducing the
need for ventilation (e.g., mechanical ventilation), or a
combination thereof. For example, an ethanol product may be applied
to airways of patients having coronavirus or have been exposed to
coronavirus.
[0005] The methods described herein may also be counterintuitive
because alcohol intake is a well-known risk factor for developing
lung infections; heavy alcohol consumption impairs lung defenses.
Alcohol consumption is believed associated with prolonged cough and
bronchitis. Moreover, alcohol itself is an ablative agent, when
injected into tissues and nerves (e.g., alcohol septal ablation or
therapeutic neurolysis).
[0006] The respiratory tract includes the upper respiratory system;
the upper airways (e.g., the oral cavity, nasal cavity,
nasopharynx, oropharynx, laryngopharynx, larynx, and top of the
trachea). The lower airways or lower respiratory tract includes the
trachea, the bronchi; upper and middle and lower lobes of the lung;
bronchioles and alveoli. There may be some overlap of the trachea
in these upper and lower airways definitions.
[0007] The described methods may be applied to people having
SARS-CoV-2, or other viral and/or bacterial exposure, other than
coronavirus or coronavirus exposure, or comorbid with coronavirus
or coronavirus exposure. For example, the patient may be exposed to
SARS-CoV-2 and/or have COVID-19 disease comorbid with an additional
or different viral or bacterial infection. Additional or different
viral or bacterial infections and infection combinations are within
the scope of this disclosure. For example, infections and
combinations of infections that include any of a coronavirus, an
influenza virus, and/or bacterial pneumonia (e.g., Streptococcus
pneumoniae), etc. The described methods may be applied to any
primary and/or secondary infection that negatively impacts the
airways, and particularly, the lungs.
[0008] For example, SARS-CoV-2 is often spread by coughing or
sneezing, which releases tiny, virus laden droplets in the air that
are inhaled by others in proximity. The infection may begin in the
upper airways, such as mucous membranes in the nasal passages and
in the back of the throat; then spreads down into the lower
airways. The virus attacks the respiratory mucosa. The ability to
disinfect these respiratory mucosa and/or prevent (further) spread
of the infectious agent (e.g., SARS-CoV-2) may be the difference
between life and death in some cases, and may greatly reduce the
transmission to others.
[0009] The delivery of alcohol (e.g., ethanol) and/or other active
ingredients or agents of the described methods include delivery to
the airways by spraying, dispensing, dripping, aerosolization,
nebulization, delivery that includes application of positive
pressure with a positive pressure device (e.g., intermittent
positive pressure breathing device), and/or delivery that includes
manual and/or mechanical ventilation, or any combination thereof. A
positive pressure device can help push the alcohol (e.g., ethanol)
further into the lungs. Positive pressure may facilitate this
transport with a therapeutic gas, such as oxygen, to the alveolar
region.
[0010] In some embodiments, an incentive device and/or inhalation
resistance device is used as a nebulizer accessory, or a nebulizer
with resistance settings (e.g., U.S. Pat. No. 9,757,528), may help
enhance aerosol entrainment and delivery to deeper reaches of the
lung, and provide pulmonary physiotherapy. Some devices may also
provide positive expiratory pressure and/or airway vibrations to
help dislodge and/or remove mucous secretions in the airways, but
also to help the patient exhale more of their carbon dioxide. An
incentive spirometer with positive expiratory pressure features for
use with a nebulizer can be ideal in some embodiments.
[0011] The alcohol (e.g., ethanol) may be delivered with one or
more other active ingredients or agents, such as one or more of
each of a bronchodilator (e.g., beta-adrenergic bronchodilators
like salbutamol [albuterol], pirbuterol, and terbutaline, or
possibly anticholinergic bronchodilators, such as ipratropium
bromide), a surfactant (e.g., calfactant), an anti-viral drug
(e.g., remdesivir), an antibacterial drug (e.g., azithromycin), an
anti-inflammatory drug (e.g., hydroxychloroquine, fluticasone or
other steroid or non-steroidal drug), an anti-clotting drug or
anticoagulant therapy (e.g., heparin, tissue plasminogen
activator), a cytokine (e.g., interferon beta), a cytokine
inhibitor, an interleukin, an interleukin inhibitor, other drugs,
or any combination thereof. These examples are not meant to be
limiting. In other embodiments, the above active ingredients may be
delivered separately or sequentially from the alcohol delivery.
Some active ingredients can be delivered directly to the lungs,
while other may be delivered by other routes, such as oral or
intravenous routes. For example, remdesivir (e.g., 200 mg on day
one and 100 mg for several days to over a week) may be delivered
intravenously to severe COVID-19 patients.
[0012] Some infections and diseases, such as COVID-19, are
associated with blood clots. Blood clots can form in appendages,
which require amputation. Blood clots can also form in the small
vessels of the lungs, leading to pulmonary embolism and respiratory
failure. Alcohol (e.g., ethanol) has some blood thinning properties
and is suspected of reducing clotting processes. It is believed
that the methods of this disclosure, such as of delivering alcohol
(e.g., ethanol) into the lungs, may help break up blood clot
formation in the lungs and/or help prevent blood clotting in the
lungs. Furthermore, additional anti-clotting treatments and/or
drugs, delivered systemically and/or delivered into the lungs with
these methods may greatly help these patients.
[0013] A bronchodilator (e.g., 2.5 to 5 mg of salbutamol) may be
delivered sequentially or simultaneously with ethanol to counter
some of ethanol's suspected pulmonary vasoconstricting properties.
In some instances, ethanol may stimulate the bronchodilation.
Ingestion of alcohol is known to treat and to cause asthmatic
episodes. Inhalation of ethanol has been known to cause irritation
and even bronchospasm, although may also relax bronchial smooth
muscle. So ethanol has opposing effects, some of which may involve
its metabolites (e.g., acetaldehyde).
[0014] For COVID-19, a disease marked by alveolar inflammation and
low oxygen saturation; treatment to the deepest parts of the lungs
may be desirable. The alveoli are where gas exchange takes place in
the lungs. The SARS-CoV-2 virus tends to clog these alveoli, such
as with virus laden secretions, dead lung cells, and possibly with
immune cells as well. The presence of these substances in the
alveoli can interfere with the diffusion of oxygen, which
epithelial cells lining the alveoli depend. Anoxic epithelium can
become more permeable to fluids. A froth may develop from labored
breathing which further blocks oxygenation of the alveolar
epithelium. In some examples, a secondary effect of these methods
involving alcohol is to separate or disrupt this froth, if present.
However, it is noted that ethanol can be suspected of having some
pulmonary vasoconstricting properties and in some situations, can
induce pulmonary edema; even though ethanol has been tried for
treating pulmonary edema in the past decades ago. Ethanol is
believed to have potential for stabilizing lung surfactant.
[0015] It may be desirable to have the alcohol (e.g., ethanol)
delivered along with oxygen gas for inhalation. In other
embodiments, the alcohol (e.g., ethanol) is delivered with
compressed air or other medical gas. For example, a humidifier or
humidifier jar can administer ethanol vapor while connected to an
oxygen gas supply or flowmeter. Generally, at least 10% ethanol
should be placed in the humidifier bottle, and 70% up to absolute
ethanol or dehydrated alcohol (e.g., 95% ethanol or more) may be
used. It is generally believed that lower concentrations of 10% to
30% are more tolerable with less irritation. Alcohol can irritate
the bronchial mucosa. However, higher concentrations (e.g., above
30%, such as 50%, 70% or 95%) may be more denaturing and virucidal.
For example, 70% ethanol in water or saline can be placed in a
humidifier jar with an oxygen gas flow rate of 2 liters per minute
up to 16 liters per minute. In other examples, high flow oxygen
systems (up to 60 liters per minute of oxygen) can be used. It is
generally recommended that the concentration of ethanol be reduced
as the oxygen flow rate increases and/or as the treatment time
increases. Treatment times can vary from minutes to over an hour.
In some embodiments, warm humidified alcohol solution can be
administered and/or a warming humidifier and/or a humidifier bottle
warmer can be used when delivering humidified alcohol solution for
inhalation, such as with medical gas (e.g., oxygen gas) delivery.
Warming inhalation droplets can be more comfortable and prevent
drying of the airways, but may also improve (e.g., reduce) particle
size for inhalation.
[0016] In other examples, ethanol can be delivered by a jet
nebulizer while connected to oxygen gas, which operates the jet. In
these implementations, oxygen saturation can improve immensely when
the liquid ethanol or ethanol solution is inhaled via mouthpiece or
by face mask/aerosol mask or by nasal cannula. Compressed air or
other medical gas may operate the jet nebulizer. There exist small
volume and large volume nebulizers. Alcohol (e.g., ethanol) can
also be delivered via an anesthesia mask. In addition to
disinfecting the lungs, inhaled ethanol may also break up phlegm
and improve expectorate as another advantage. There also exist
nebulizer warmers/heaters that can be used in some embodiments to
heat the aerosols.
[0017] Nebulizers and humidifiers can be used in mechanical
ventilation circuits as well.
[0018] Hydrogen gas is another medical gas that may also be desired
for delivery to the lungs, with or without concomitant oxygen gas
therapy. Hydrogen gas can also be delivered via a jet nebulizer or
mask or nasal cannula, for example. It is believed that hydrogen
gas may reduce some of the hyperoxic lung injury; damage that
concentrated oxygen causes to lungs, especially of critically ill
patients receiving oxygen gas for extended periods of time, which
can lead to respiratory failure. Hydrogen gas has antioxidant and
anti-inflammatory effects. Hydrogen gas is believed to protect the
lungs at least by regulation of protective proteins, such as by
induction and/or activation of heme-oxygenase-1 enzyme.
Importantly, hydrogen gas therapy is believed to eliminate toxic
reactive oxygen species, such as cytotoxic oxygen radicals; which
may accompany inflammation. Reactive oxygen species may constrict
airway smooth muscle. These methods utilize hydrogen gas to counter
the reactive oxygen species generated from infection-related
inflammation in the lungs and/or from oxygen therapy itself.
Hydrogen gas may also reduce acute lung injury caused by mechanical
ventilation.
[0019] Therapeutic gases, such as oxygen and/or hydrogen can also
or alternatively be delivered to the airways and/or lungs via
liquid solution, such as when the solution is hyperoxygenated
and/or hyperhydrogenated. In such embodiments, the liquid solution
can contain the alcohol (e.g., ethanol) as well.
[0020] Note that ethanol is flammable. Ethanol at 30% is believed
flammable at room air, while ethanol at 25% is believed flammable
in oxygen. At lower concentrations, ethanol loses its flammability.
Caution in storing and using alcohol (e.g., ethanol) is advised,
such as keeping away from sources of heat or flame.
[0021] In some examples, at least 0.1 mL of alcohol (e.g., ethanol)
product or solution may be administered to the upper airways, such
as intranasally; e.g., with a nasal spray pump or MDI. For
nebulization, an at least 1 mL of ethanol product or solution may
be delivered. In some examples, 3 mL or more of ethanol product or
solution may be nebulized. An ultrasonic nebulizer can also be used
instead of a jet nebulizer, in some examples.
[0022] Ethanol inhalation or delivery to airways should be done
under the supervision and/or advice of a healthcare practitioner.
Generally, nebulizers and other aerosol delivery devices require a
prescription. Some nebulizers may have a filter accessory to reduce
exposure, (e.g., occupational exposure) to those present in the
room.
[0023] Other aerosolization devices may also be used. For example,
a metered dose intranasal inhaler may be used to deliver alcohol
(e.g., ethanol) product or solution droplets to the nasal cavity
for sterilization or disinfection of viral load there. Such methods
may also reduce the amount of live virus spread to others.
[0024] It is to be understood that in many embodiments, the alcohol
(e.g., ethanol) is not an excipient ingredient, but rather an
active ingredient of the liquid when utilized in many of these
methods. Example excipient ingredients may include glycerin, salts
like sodium chloride and potassium bicarbonate, detergents and/or
chelators such as EDTA, certain polymers, pH adjustors (e.g., acids
or bases), liposomes, preservatives, solvents or water. These
classes of excipients and/or excipient examples are not meant to be
limiting. Pharmaceutically acceptable excipients are preferred.
[0025] In some embodiments of these methods, a pulmonary catheter
may be used to dispense ethanol product or solution to the airways
or lungs. If inhalation of aerosol (e.g., via a mouthpiece) does
not reach the alveolar region; dispensing to or near the alveolar
region of the lungs can be possible with such an intrapulmonary
catheter. This procedure generally may involve bronchoscopy. A
fiber-optic bronchoscope device would be desirable in this case,
and visualization and/or imaging may be helpful. In some
embodiments of these methods, the catheter dispenses or sprays the
ethanol containing liquid. In other embodiments to these methods,
the catheter includes a tiny intrapulmonary aerosol generation
device associated with the catheter and is placed down into the
lungs to deliver aerosol directly to the desired regions of the
lungs. Some embodiments of these methods rely on performing an
endoscopy, including rhinoscopy, laryngoscopy, bronchoscopy, or a
combination thereof, to visualize the upper and/or lower airways
and/or to apply the alcohol (e.g., ethanol) to the upper and/or
lower airways.
[0026] Dilution of the liquid ethanol product or solution, such as
with water, saline, and/or other drug solution may be generally
desirable. A final ethanol product or solution dilution of 30%,
40%, 50%, 60% or 70%, or even above 70% (e.g., 80%) may be
preferred. It is believed that pure ethanol is less effective than
diluted ethanol because water aids in the denaturation of proteins,
which is believed the mode of action for alcohol's disinfectant
activity. However, the lungs contain fluid too, at least on its
mucosa surface, which can dilute alcohol further. Too much dilution
of alcohol may reduce or eliminate alcohol's virucidal/bactericidal
activity. It is believed that a final ethanol concentration of 60%
to 80% has potent virucidal activity. Yet, too strong a
concentration of ethanol could destroy lung tissue. Injection of
concentrated ethanol is ablative to tumors, nerves, and other
tissues. So finding the right balance between having some virucidal
and/or bactericidal activity, and minimizing tissue damage, may be
essential with the methods described herein. In some examples,
preparation of treatment protocols according to these methods may
be further refined and/or customized based on an individual
patient's needs. In other embodiments, the final ethanol product or
solution dilution may be below 30% alcohol.
[0027] Exposure time for the virucidal and/or bactericidal agent,
such as alcohol, is another factor. A minimum exposure time may be
needed, which can be on the order of a few seconds (e.g., at or
around 15 seconds) or on the order of several minutes (e.g., more
than 5 minutes). These are nonlimiting examples. The proper
exposure time to the alcohol and/or other virucidal and/or
bactericidal agent in the airways may depend on the patient, his or
her condition, level of mucous secretions, etc. Exposure time may
have to be adapted during the time of each procedure until more
standardized protocols are developed for these methods.
[0028] In some examples, a bronchoalveolar lavage (e.g., lung
lavage or lung washing) procedure may be used to provide the
ethanol product or solution to the infected patient's lung to wash
out the lung and to disinfect and reduce a viral load in the
patient's lungs of an infected patient. In some examples, whole
lung lavage is desirable. Candidates for this procedure may have
experienced a decline in lung function, a decline in partial
pressure of oxygen (e.g., to less than 70 mmHg), a decline in
diffusing capacity of the lungs for carbon monoxide, a decline in
forced vital capacity, a decline in peripheral capillary oxygen
saturation, or a combination thereof. Worsening of lung function of
candidates for this procedure may also be determined based on
imaging of the lungs and/or chest, e.g., a chest X-ray or a
computed tomography.
[0029] During the lung lavage procedure, generally a bronchoscope
is passed through the mouth, trachea, or nose and into an
appropriate airway in the lungs. The patient is typically
anesthetized under general anesthesia during the procedure to
mitigate discomfort and to improve the likelihood that the patient
will remain still during the procedure. In some examples, one lung
is washed at a time, although both lungs can often be lavaged
sequentially in the same treatment session, or in different
sessions. It may be advisable to perform the lavage on the most
severely affected lung first. In other examples, both lungs may be
lavaged simultaneously, although this is less common as it
typically requires extracorporeal membrane oxygenation (an
artificial lung for heart-lung bypass support). Extracorporeal
membrane oxygenation may be required for more severe patients as
well.
[0030] In this disclosure, an alcohol (e.g., ethanol) product or
solution is used for, or to make, at least some portion of the lung
lavage wash solution in this procedure and is preferably in normal
saline. In some examples, the alcohol (e.g., ethanol) product or
solution may be warmed to around 37 degrees Celsius (e.g., body
temperature). In some examples, only one or a few lung volumes of
lung wash solution contains ethanol. In other examples, most or all
of the lung wash solution volume contains the ethanol. The alcohol
(e.g., ethanol) comprising the lung wash solution is at a
concentration of at least 5% volume by volume of solution, and
preferably above 10% volume by volume of solution. Ethanol is also
sometimes measured as weight per volume of solution. In some
examples, the total lung wash solution volume used is 20 to 30
liters, and up to 50 liters in extreme cases. Therefore, in most
examples, at least a half-liter of ethanol-containing lung wash
solution is used. In some examples, one liter of ethanol-containing
lung wash solution is used. In still further examples, two or more
liters of ethanol-containing lung wash solution is used. It is
useful to select an alcohol and salt concentration for the aqueous
wash solution or tincture wash solution that does not cause the
alcohol to become appreciably immiscible in water. Mixing of the
alcohol-containing wash solution may be appropriate in some
examples. Because of potential salting out, alcohol may not be
intuitive to use with saline.
[0031] Generally, the wash solution is allowed to flow by gravity
(or hydrostatic pressure) into the lung. In some examples, the lung
or lungs are filled with wash solution to functional residual
capacity, with repeated cycles of instillation and drainage. The
initial instillation in some examples is half the functional
residual capacity. In other examples, incremental tidal volumes of
a half-liter to one liter, or simply one-liter aliquots, of wash
solution are instilled. These examples are not meant to be
limiting. As solution and effluent is brought out (e.g., suctioned
out) of the lungs, initial volumes may be opaquer and less clear,
as they contain more mucous and/or deposits. During the procedure,
physiotherapy/physical therapy of the thorax and/or chest, manually
or with a shaking device or vest, helps agitate the lungs and lung
wash to remove more deposits. So chest percussion may be used at
both maximal wash volume and during draining, for each cycle. For
example, multiple cycles of lung instillation (with of a tidal
volume of a half-liter to full liter of warmed wash solution),
chest percussion therapy (for a couple minutes; 2 to 5 minutes),
and removal of fluid from the lung (by active suction and or
drainage) is performed repeatedly; generally until the lavage
effluent is clear. Lung ventilation is used during this procedure,
as is patient monitoring, such as of vital signs. Pulse oximetry
and even serial readings of arterial blood gas levels are checked
regularly during this procedure.
[0032] A lung lavage wash solution could be hyperoxygenated and/or
hyperhydrogenated before use to enhance treatment with these
methods. For instance, hyperoxygenated solution may improve oxygen
supply and reduce hypoxemia during the procedure. Such solutions
can be aerated with oxygen until pressure in its container or bag
reaches 1000 mmHg, then warmed to 37 degrees Celsius, prior to
lavage use.
[0033] In some examples, application of an alcohol (e.g., ethanol)
product or solution is administered to the lungs and/or airways
prior to, during, and/or after a lung lavage. Suction with a
suction device into a specimen collection trap, or collection with
a syringe, can remove viral containing fluids and secretions.
Applying of the ethanol product or solution to the lungs and/or
airways after the lung lavage can help ensure disinfection of the
lungs and/or airways and viral load reduction.
[0034] Specimen collection from the lung lavage can be used for
testing lung fluid and/or lung secretions for virus quantitatively
and/or qualitatively, before and/or after the lung lavage
procedure; and in most cases, to note a reduction of viral load. In
other examples, bacteria and/or fungus in the lung fluid and/or
lung secretions may also or alternatively be tested quantitatively
and/or qualitatively. Identification of the type of virus and/or
bacteria and/or fungus may be beneficial. In some embodiments,
identification of the contagion is achieved by antibody binding
assays and/or genetic sequencing.
[0035] Alcohol-containing lavage wash solutions may also be used in
other embodiments, including for pharyngeal lavage and/or nasal
lavage (e.g., nasal irrigation). These other embodiments may also
disinfect and/or clean out these regions of mucous and contagion.
Fluids and/or secretions contained by these other lavages or washes
may also be collected and tested for contagion quantitatively
and/or qualitatively. In its simplest other embodiment,
alcohol-containing wash solution is delivered by a neti pot.
[0036] One of the goals of this disclosure is to prevent or treat
complicated pneumonia, which otherwise may require lung(s) to be
drained or diseased lung tissue to be removed in what is called
lung scraping. In some embodiments, lungs may be drained or scraped
along with these methods.
[0037] In some examples, the methods disclosed herein could be
applied to treat soldiers and military personnel that are thought
to have been exposed to infectious agents or have active
infections.
[0038] The methods disclosed herein could be applied to treat
veterinary patients or animals that are thought to have been
exposed to infectious agents or have active infections. It is
believed that zoo animals, such as tigers, had COVID-19 infection.
These methods could be applied to pets such as cats and dogs. These
methods could be applied to chimpanzees and gorillas. These methods
could be applied to endangered species. These methods could be used
to treat horses. These methods could be used to treat cattle,
swine, and other livestock that comprise our nation's food supply.
Although these methods are primarily suited for mammals, the
methods could be adapted for treating poultry and other birds.
Avian influenza and other future animal epidemics could endanger
the world's food supply, and methods for treating such or reducing
its spread could be invaluable.
[0039] In some examples, a monohydric alcohol may be used.
[0040] In some examples, a dihydric or polyhydric alcohol may be
used.
[0041] In some examples, a non-branched alcohol may be used.
[0042] In some examples, a branched alcohol may be used.
[0043] In some examples, a ringed alcohol or aromatic alcohol, such
as phenol or benzyl alcohol, may be used.
[0044] In some examples, two or more alcohol (hydroxyl) functional
groups are present, and includes diols and triols for the
alcohol.
[0045] In some examples, an alcohol derivative or conjugate (e.g.,
ethyl acetate or butyl acetate) may be used instead or in addition
to the alcohol. Alcohol derivatives or conjugates can include
esters, ethers, carboxylic acids, amides, amines, ketones, other
organic molecules, or combinations thereof.
[0046] Blood alcohol levels should be monitored to ensure that
significant absorption via the inhalation route is not taking
place, so as to avoid potential for alcohol poisoning.
[0047] The above examples are not meant to be limiting.
[0048] In some embodiments, the alcohol or alcohol product (e.g., a
liquid pharmaceutical drug composition or formulation containing
alcohol), or a dilution or solution thereof, is comprised of
fermented alcohol. For example, ethanol is often made from grain
alcohol fermentative processes.
[0049] In other embodiments, the alcohol or alcohol product (e.g.,
a liquid pharmaceutical drug composition or formulation containing
alcohol), or a dilution or solution thereof, is comprised of
synthesized alcohol. In other embodiments, the alcohol or alcohol
product (e.g., a liquid pharmaceutical drug composition or
formulation containing alcohol), or a dilution or solution thereof,
is comprised of fermented alcohol and synthesized alcohol. For
example, the alcohol or alcohol product (e.g., a liquid
pharmaceutical drug composition or formulation containing alcohol),
or a dilution or solution thereof, is comprised of fermented and/or
synthesized ethanol. Chemical synthesis of ethanol can involve the
acid-catalyzed hydration of ethylene. In these examples,
distillation and dehydration of alcohol may be used to increase the
purity of the alcohol. Up to and over 99% pure ethanol can be
achievable for the alcohol in some embodiments.
[0050] The disclosed methods can be combined with other
disinfecting and treatment methods, such as using virucidal and/or
bactericidal wavelengths of light shone inside the lungs from a
source of light (e.g., via fiber optic(s) and/or associated with a
modified bronchoscope) placed down into the lungs.
Examples
[0051] Example 1 is a method, comprising: applying an at least one
alcohol as a liquid, solution, or pharmaceutical drug composition
to upper and/or lower airways of a person or animal exposed to an
infectious agent.
[0052] In Example 2, the subject matter of Example 1 additionally
or alternatively includes, wherein the upper and/or lower airways
of the person or animal exposed to the infectious agent are
disinfected in response to application of the at least one alcohol
to the upper and/or lower airways of the person or animal.
[0053] In Example 3, the subject matter of any of Examples 1-2
additionally or alternatively includes, wherein a viral load in the
upper and/or lower airways of the person or animal exposed to the
infectious agent is reduced in response to application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
[0054] In Example 4, the subject matter of any of Examples 1-3
additionally or alternatively includes, treating the person or
animal exposed to the infectious agent via application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
[0055] In Example 5, the subject matter of any of Examples 1-4
additionally or alternatively includes, reducing or eliminating
blood clots of the person or animal exposed to the infectious agent
in response to application of the at least one alcohol to the upper
and/or lower airways of the person or animal.
[0056] In Example 6, the subject matter of any of Examples 1-5
additionally or alternatively includes, improving respiration of
the person or animal exposed to the infectious agent via
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
[0057] In Example 7, the subject matter of any of Examples 1-6
additionally or alternatively includes, improving oxygen saturation
of the person or animal exposed to the infectious agent via
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
[0058] In Example 8, the subject matter of any of Examples 1-7
additionally or alternatively includes, preventing a need for
mechanical ventilation of the person or animal exposed to the
infectious agent via application of the at least one alcohol to the
upper and/or lower airways of the person or animal.
[0059] In Example 9, the subject matter of any of Examples 1-8
additionally or alternatively includes, reducing a length of time
the person or animal exposed to the infectious agent needs
mechanical ventilation in response to application of the at least
one alcohol to the upper and/or lower airways of the person or
animal.
[0060] In Example 10, the subject matter of any of Examples 1-9
additionally or alternatively includes, wherein the at least one
alcohol includes ethanol.
[0061] In Example 11, the subject matter of any of Examples 1-10
additionally or alternatively includes, wherein the at least one
alcohol includes propanol or isopropyl alcohol.
[0062] In Example 12, the subject matter of any of Examples 1-11
additionally or alternatively includes, wherein the at least one
alcohol includes phenol.
[0063] In Example 13, the subject matter of any of Examples 1-12
additionally or alternatively includes, wherein an at least one
alcohol derivative or conjugate is used instead of or in addition
to said at least one alcohol.
[0064] In Example 14, the subject matter of any of Examples 1-13
additionally or alternatively includes, nebulizing or aerosolizing
the at least one alcohol, or humidifying therapeutic gas with the
at least one alcohol, for application to the upper and/or lower
airways of the person or animal.
[0065] In Example 15, the subject matter of any of Examples 1-14
additionally or alternatively includes, spraying, dispensing, or
dripping the at least one alcohol for application of the at least
one alcohol to the upper and/or lower airways of the person or
animal.
[0066] In Example 16, the subject matter of any of Examples 1-15
additionally or alternatively includes, performing an endoscopy,
including rhinoscopy, laryngoscopy, bronchoscopy, or a combination
thereof, to apply the at least one alcohol to the upper and/or
lower airways of the person or animal.
[0067] In Example 17, the subject matter of any of Examples 1-16
additionally or alternatively includes, performing a lavage, a
bronchoalveolar lavage, or a whole lung lavage to apply the at
least one alcohol to the upper and/or lower airways of the person
or animal.
[0068] In Example 18, the subject matter of any of Examples 1-17
additionally or alternatively includes, removing a majority of the
at least one alcohol from the upper and/or lower airways of the
person or animal after application of the at least one alcohol to
the upper and/or lower airways of the person or animal.
[0069] In Example 19, the subject matter of any of Examples 1-18
additionally or alternatively includes, removing fluid and/or
mucous from the upper and/or lower airways of the person or animal
after application of the at least one alcohol to the upper and/or
lower airways of the person or animal.
[0070] In Example 20, the subject matter of any of Examples 1-19
additionally or alternatively includes, intubating the person or
animal exposed to the infectious agent after or during application
of the at least one alcohol to the upper and/or lower airways of
the person or animal.
[0071] In Example 21, the subject matter of any of Examples 1-20
additionally or alternatively includes, diluting the at least one
alcohol prior to application of the at least one alcohol to the
upper and/or lower airways of the person or animal.
[0072] In Example 22, the subject matter of any of Examples 1-21
additionally or alternatively includes, diluting the at least one
alcohol with water and/or saline prior to application of the at
least one alcohol to the upper and/or lower airways of the person
or animal.
[0073] In Example 23, the subject matter of any of Examples 1-22
additionally or alternatively includes, diluting the at least one
alcohol with a bronchodilator-containing solution prior to
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
[0074] In Example 24, the subject matter of any of Examples 1-23
additionally or alternatively includes, diluting the at least one
alcohol with surfactant-containing solution prior to application of
the at least one alcohol to the upper and/or lower airways of the
person or animal.
[0075] In Example 25, the subject matter of any of Examples 1-24
additionally or alternatively includes, diluting the at least one
alcohol to contain between and including 5% to 95% alcohol or
ethanol prior to application of the at least one alcohol to the
upper and lower airways of the person or animal.
[0076] In Example 26, the subject matter of any of Examples 1-25
additionally or alternatively includes, diluting the at least one
alcohol to contain from 30% to 70% alcohol or ethanol prior to
application of the at least one alcohol to the upper and/or lower
airways of the person or animal.
[0077] In Example 27, the subject matter of any of Examples 1-26
additionally or alternatively includes, mixing the at least one
alcohol with an at least one additional active pharmaceutical
ingredient and/or active pharmaceutical ingredient formulation
prior to application of the at least one alcohol to the upper
and/or lower airways of the person or animal.
[0078] In Example 28, the subject matter of any of Examples 1-27
additionally or alternatively includes, wherein the at least one
alcohol includes a liquid pharmaceutical drug formulation having an
at least one excipient ingredient and an at least one active
pharmaceutical ingredient.
[0079] In Example 29, the subject matter of any of Examples 1-28
additionally or alternatively includes, sampling and testing lung
fluid and/or lung secretions for infectious agent quantitatively
and/or qualitatively prior to and/or after application of the at
least one alcohol to the upper and lower airways of the person or
animal.
[0080] In Example 30, the subject matter of any of Examples 1-29
additionally or alternatively includes, wherein the infectious
agent includes a bacteria and/or fungus.
[0081] In Example 31, the subject matter of any of Examples 1-30
additionally or alternatively includes, wherein the infectious
agent includes a virus and a bacteria.
[0082] In Example 32, the subject matter of any of Examples 1-31
additionally or alternatively includes, wherein the infectious
agent includes a virus.
[0083] In Example 33, the subject matter of Example 32 additionally
or alternatively includes, wherein the virus includes a
coronavirus.
[0084] In Example 34, the subject matter of any of Examples 32-33
additionally or alternatively includes, wherein the virus includes
a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
[0085] In Example 35, the subject matter of any of Examples 1-34
additionally or alternatively includes, wherein the person or
animal is a COVID-19 patient.
[0086] In Example 36, the subject matter of any of Examples 1-35
additionally or alternatively includes, wherein the animal is a
veterinary patient.
[0087] In Example 37, the subject matter of any of Examples 1-36
additionally or alternatively includes, applying at least 0.1 mL of
the at least one alcohol to the upper and/or lower airways of the
person or animal.
[0088] In Example 38, the subject matter of any of Examples 1-37
additionally or alternatively includes, applying at least 1 mL of
the at least one alcohol to the upper and/or lower airways of the
person or animal.
[0089] In Example 39, the subject matter of any of Examples 1-38
additionally or alternatively includes, applying the at least one
alcohol to the upper and/or lower airways of the person or animal
using positive-pressure or a positive-pressure device.
[0090] In Example 40, the subject matter of any of Examples 1-39
additionally or alternatively includes, applying the at least one
alcohol to the upper and/or lower airways of the person or animal
while using an incentive device and/or inhalation resistance
device.
[0091] In Example 41, the subject matter of any of Examples 1-40
additionally or alternatively includes, wherein the at least one
alcohol as a liquid, solution, or pharmaceutical drug composition
comprises at least 10% alcohol or ethanol.
[0092] Example 42 is a lung lavage wash solution comprising at
least 10% alcohol or ethanol diluted in saline.
[0093] Various illustrative components, blocks, configurations,
modules, and steps have been described above generally in terms of
their functionality. Persons having ordinary skill in the art may
implement the described functionality in varying ways for each
particular application, but such implementation decisions should
not be interpreted as causing a departure from the scope of the
present disclosure.
[0094] The previous description of the disclosed embodiments is
provided to enable a person skilled in the art to make or use the
disclosed embodiments. Various modifications to these embodiments
will be readily apparent to those skilled in the art, and the
principles defined herein may be applied to other embodiments
without departing from the scope of the disclosure. Thus, the
present disclosure is not intended to be limited to the embodiments
shown herein but is to be accorded the widest scope possible
consistent with the principles and novel features as previously
described.
* * * * *